Submissions for variant NM_001354604.2(MITF):c.366C>T (p.His122=)

gnomAD frequency: 0.00201  dbSNP: rs140663277

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217396	SCV000269242	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	His122His in exon 3 of MITF: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 0.3% (30/8600) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs140663277).
Illumina Laboratory Services, Illumina	RCV000332499	SCV000445918	benign	Tietz syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000382353	SCV000445919	benign	Waardenburg syndrome type 2A	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586833	SCV000696087	benign	not provided	2016-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000586833	SCV000730723	benign	not provided	2019-02-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086789	SCV001001254	benign	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2025-02-04	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000586833	SCV001144510	benign	not provided	2019-02-21	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000217396	SCV002071070	benign	not specified	2021-09-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257516	SCV002536415	benign	Hereditary cancer-predisposing syndrome	2020-10-09	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000217396	SCV002550858	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586833	SCV002563776	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	MITF: BP4, BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316182	SCV004015852	benign	Melanoma, cutaneous malignant, susceptibility to, 8	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586833	SCV005264089	likely benign	not provided		criteria provided, single submitter	not provided
Ambry Genetics	RCV002257516	SCV005444984	likely benign	Hereditary cancer-predisposing syndrome	2024-10-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003891791	SCV000303137	benign	MITF-related disorder	2020-07-20	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586833	SCV001971023	likely benign	not provided		no assertion criteria provided	clinical testing